Retrospective analysis of institutional scabies outbreaks from 1984 to 2013: lessons learned and moving forward.

Scabies outbreaks can be disruptive in institutional settings, and are associated with considerable but under-researched morbidity, especially in vulnerable populations. In this paper, we describe key findings from a retrospective review of scabies outbreaks reported in the literature over the past 30 years. We undertook this review to gain insights into the impact of institutional outbreaks, the burden in terms of attack rates, economic costs, treatment trends, the types of index cases and outbreak progression. We found 84 reports over 30 years, with outbreaks most frequently reported in aged care facilities (n = 40) and hospitals (n = 33). On average, scabies outbreaks persisted for 3 months, and the median attack rate was 38%. While 1% lindane was once the most commonly employed acaricide, 5% permethrin and oral ivermectin are increasingly used. Crusted scabies represented the index case for 83% of outbreaks, and scabies was misdiagnosed in 43% outbreaks. The frequency of reported scabies outbreaks has not declined consistently over time suggesting the disease is still highly problematic. We contend that more research and practice emphasis must be paid to improve diagnostic methods, surveillance and control, health staff education and management of crusted scabies to prevent the development of scabies outbreaks in institutional settings.

Crusted scabies is associated with increased IL-17 secretion by skin T cells.

Scabies is an ectoparasitic infestation by the mite Sarcoptes scabiei. Although commonly self-limiting, a fraction of patients develop severely debilitating crusted scabies. The immune mechanisms underlying the development of crusted scabies are unclear, and undertaking longitudinal infection studies in humans is difficult. We utilized a porcine model to compare cellular immune responses in peripheral blood and skin of pigs with different clinical manifestations of scabies (n = 12), and in uninfected controls (n = 6). Although clinical symptoms were not evident until at least 4 weeks post-infestation, the numbers of peripheral IFNγ-secreting CD4(+) T cells and γδ T cells increased in infected pigs from week 1 post-infestation. γδ T cells remained increased in the blood at week 15 post-infestation. At week 15, skin cell infiltrates from pigs with crusted scabies had significantly higher CD8(+) T cell, γδ T cell and IL-17(+) cell numbers than those with ordinary scabies. Peripheral IL-17 levels were not increased, suggesting that localized skin IL-17-secreting T cells may play a critical role in the pathogenesis of crusted scabies development. Given the potential of anti-IL-17 immunotherapy demonstrated for other inflammatory skin diseases, this study may provide a novel therapeutic avenue for patients with recurrent crusted scabies.

Correction: Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia.

Following the publication of this article the authors noted that data describing precisely where phosphorylation sites in proteins modulated following JAK1 or JAK3 inhibition in mutant T-ALL samples was not clearly annotated. Therefore an additional sheet has been added to Supplementary Table 2.

Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia.

Mutations in the interleukin-7 receptor (IL7R) or the Janus kinase 3 (JAK3) kinase occur frequently in T-cell acute lymphoblastic leukemia (T-ALL) and both are able to drive cellular transformation and the development of T-ALL in mouse models. However, the signal transduction pathways downstream of JAK3 mutations remain poorly characterized. Here we describe the phosphoproteome downstream of the JAK3(L857Q)/(M511I) activating mutations in transformed Ba/F3 lymphocyte cells. Signaling pathways regulated by JAK3 mutants were assessed following acute inhibition of JAK1/JAK3 using the JAK kinase inhibitors ruxolitinib or tofacitinib. Comprehensive network interrogation using the phosphoproteomic signatures identified significant changes in pathways regulating cell cycle, translation initiation, mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling, RNA metabolism, as well as epigenetic and apoptotic processes. Key regulatory proteins within pathways that showed altered phosphorylation following JAK inhibition were targeted using selumetinib and trametinib (MEK), buparlisib (PI3K) and ABT-199 (BCL2), and found to be synergistic in combination with JAK kinase inhibitors in primary T-ALL samples harboring JAK3 mutations. These data provide the first detailed molecular characterization of the downstream signaling pathways regulated by JAK3 mutations and provide further understanding into the oncogenic processes regulated by constitutive kinase activation aiding in the development of improved combinatorial treatment regimens.

Imposed running exercise does not alter cell proliferation in the neurogenic niches of young lambs.

Neurogenesis, the process by which neurons are generated in the brain from progenitor cells, occurs in the subventricular zone (SVZ) and the subgranular zone (SGZ) in the adult human brain. Recently, rodent studies have demonstrated that exercise can increase neurogenesis in the SGZ; however, it is unclear if exercise also has this effect in more complex mammalian brains. The overarching aim of this study was to explore whether exercised-induced neurogenesis occurs in larger mammalian brains more representative of human brains and to explore the use of a model for exercising large animals such as sheep. For these studies, 6 male twin lambs had a structured exercise regime for 4 wk and 6 other twin male lambs were kept in an open field pen. All lambs were injected with bromodeoxyuridine (BrdU), a thymidine analog that is incorporated into the DNA of proliferating cells. Immunoperoxidase was used to visualize and quantify BrdU-positive cells in the SVZ and SGZ. Overall, no significant change in the number or distribution of BrdU-positive cells was observed in the lamb SVZ and SGZ with exercise or colabeling of BrdU with mature neuronal or glial markers in the exercised and nonexercised lamb SVZ and SGZ. Overall, this study provides a novel methodology to investigate the effects of imposed exercise on large animals and exercise-induced neurogenesis in animals with gyrencephalic brains.

Radioimmunoassay for medroxyprogesterone acetate (Provera) using the 11alpha-hydroxy succinyl conjugate.

PIP: The development of a radioimmunoassay for medroxyprogesterone acetate (MPA) employing rabbit antibodies made against a bovine serum albumin (BSA) conjugate of the hemisuccinate ester of 11alpha-hydroxy MPA are described. The 11alpa-hydroxyl group was introduced into MPA by a series of chemical and microbiological transformations. The acid succinate MPA was coupled to BSA by reacting it with N,N'-carbonyldiimidazole. Cross-reactivities of several MPA analogs were compared suing rabbit antisera developed against the C-11 conjugate of MPA and goat antiserum developed against a C-3 conjugate of MPA. Antibodies formed against the C-11 conjugate showed increased specificity to steroid analogs which changes in the C-21 side chain. The profiles of serum MPA levels vs time, measured with both the C-3 and C-11 antisera, after oral drug administration to the monkey were similar. After intramuscular drug administration to dogs, serum MPA levels measured with the C-3 antisera were consistently greater as compared with those with C-11 antisera. Factors affecting precipitation of the antibody-antigen complex, assay precision, and assay sensitivity were evaluated.^ieng

Intestinal absorption of 5 chromium compounds in young black ducks (Anas rubripes).

An in vivo intestinal perfusion technique was used to measure the absorption rates of five Cr compounds in black ducks. Cr was absorbed from saline solutions of KCr(SO4)2 and CrO3 at a rate about 1.5 to 2.0 times greater than from solutions of Cr, Cr(NO3)3, and Cr(C5H7O2)3. These results suggest the ionic form of Cr in solution may be an important factor in determining absorption of Cr compounds from the small intestine.

Enzyme activities in plasma, kidney, liver, and muscle of five avian species.

Activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH) were determined in plasma, kidney, liver, and muscle from five species of captive birds. Few differences occurred in plasma activities between sexes but considerable differences occurred between species. All five enzymes were detected in each of the tissues sampled. Relative enzyme activities in liver, kidney, and muscle were similar for each species. CPK activity was much higher in muscle than in liver or kidney and, of the five enzymes studied, may be the best indicator of muscle damage. Most of the other enzymes were more evenly distributed among the three tissues, and no organ-specific enzyme could be identified for liver or kidney. Because of interspecific variations in plasma enzyme activities, it is important to establish baseline values for each species to ensure accurate interpretation of results.

Effects of crude oil ingestion on avian intestinal function.

Intestinal function in mallard ducklings (Anas platyrhynchos) on a freshwater regime was studied after a 7-day dietary ingestion of 0.25% and 2.5% Prudhoe Bay crude oil (PBCO) or a 2.5% paraffin mixture with an in vivo luminal perfusion technique. Dietary ingestion of 2.5% PBCO may have an effect on the integrity of the duckling intestine. There were no significant effects of PBCO on the absorption of Na, Cl, K, or H2O compared with control animals. The ducklings fed 2.5% paraffin had a significant depression in Na and H2O absorption compared with controls. However, this depression dose not seem to be related to an effect on intestinal mucosa Na-K-ATPase activity.

Seasonal variation in diagnostic enzymes and biochemical constituents of captive northern bobwhites and passerines.

1. A variety of biochemical measurements were taken periodically in captive northern bobwhite (Colinus virginianus L.), European starlings (Sturnus vulgaris L.), red-winged blackbirds (Agelaius phoeniceus L.) and common grackles (Quiscalus quiscula L.) to determine whether baseline values remain sufficiently stable throughout the year for general clinical use in the absence of concurrent control specimens. 2. Variables included whole blood hematocrit and hemoglobin, plasma lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, creatine kinase, butyrylcholinesterase, alkaline phosphatase, glucose, albumin, total protein, creatinine, urea nitrogen, uric acid, cholesterol, and triglycerides, and brain acetylcholinesterase. Butyryl- and acetylcholinesterase were included because of their specific uses in toxicology. 3. Significant seasonal differences were detected for each of the variables except brain acetylcholinesterase in at least one of the species. Significant species differences were detected during at least one season for all of the variables measured. 4. All species were maintained outdoors, but only northern bobwhites came into reproductive condition and showed sex-differences in the clinical variables during their normal breeding season. 5. It was concluded that reference values for the 18 clinical variables measured could be calculated from our data for adult specimens of the species studied, and that results for one species cannot be extrapolated with certainty to any other species. 6. Estimated normal bounds for each of the 18 variables measured by commonly used clinical procedures are presented for reproductively quiescent northern bobwhites, European starlings, red-winged blackbirds, and common grackles.

Subchronic organophosphorus ester-induced delayed neurotoxicity in mallards.

Eighteen-week-old mallard hens received 0, 10, 30, 90, or 270 ppm technical grade EPN (phenylphosphonothioic acid O-ethyl-O-4-nitrophenyl ester) in the diet for 90 days. Ataxia was first observed in the 270-ppm group after 16 days, in the 90-ppm group after 20 days, in the 30-ppm group after 38 days; 10 ppm failed to produce ataxia. By the end of 90 days all 6 birds in the 270-ppm group exhibited ataxia or paralysis whereas 5 of 6 birds in the 90-ppm group and 2 of 6 birds in the 30-ppm group were visibly affected. Treatment with 30 ppm or more resulted in a significant reduction in body weight. Brain neurotoxic esterase activity was inhibited by averages of 16, 69, 73, and 74% in the 10-, 30-, 90-, and 270-ppm groups, respectively. Brain acetylcholinesterase, plasma cholinesterase, and plasma alkaline phosphatase were significantly inhibited as well. Distinct histopathological effects were seen in the 30-, 90-, and 270-ppm groups which included demyelination and degeneration of axons of the spinal cord. Additional ducks were exposed in a similar manner to 60-, 270-, or 540-ppm leptophos (phosphonothioic acid O-4-bromo-2,5-dichlorophenyl-O-methylphenyl ester) which resulted in similar behavioral, biochemical, and histopathological alterations. These findings indicate that adult mallards are probably somewhat less sensitive than chickens to subchronic dietary exposure to organophosphorus insecticides that induce delayed neurotoxicity.

Organophosphate inhibition of avian salt gland Na, K-ATPase activity.

1. Adult black ducks (Anas rubripes) were given freshwater or saltwater (1.5% NaCl) for 11 days and half of each group was also given an organophosphate (17 p.p.m. fenthion) in the diet on days 6-11. 2. After 11 days, ducks drinking saltwater had lost more weight and had higher plasma Na and uric acid concentrations and osmolalities than birds drinking freshwater. 3. Saltwater treatment stimulated the salt gland to increased weight and Na, K-ATPase activity. 4. Fenthion generally reduced plasma and brain cholinesterase activity and depressed cholinesterase and Na, K-ATPase activities in salt glands of birds drinking saltwater.

Do patients with ankylosing spondylitis have poorer balance than normal subjects?

OBJECTIVES: To investigate whether patients with ankylosing spondylitis have poorer balance than normal subjects, and to study the relationship between balance and posture. METHODS: Balance was studied in 30 ankylosing spondylitis subjects using sway magnetometry, making quantitative measurements of movement at the hips with eyes open and eyes closed. The results were compared with data from 58 normal subjects. Balance was also compared with quantitative measurements of posture. RESULTS: The numbers of patients with poor balance, above the 95th percentile for normal, were significantly greater than expected; 18% for eyes open (P = 0. 03) and 23% for eyes closed (P = 0.004). No significant relationships between balance and any of the quantitative descriptions of posture were demonstrated. CONCLUSION: A significant proportion of ankylosing spondylitis patients have poorer balance than normal subjects.

Biochemical and hematological effects of lead ingestion in nestling American kestrels (Falco sparverius).

One-day old American kestrel (Falco sparverius) nestlings were orally dosed daily with 5 microliters/g of corn oil (controls), 25, 125 or 625 mg/kg of metallic lead in corn oil for 10 days. Forty per cent of the nestlings receiving 625 mg/kg of lead died after 6 days and growth rates were significantly depressed in the two highest lead dosed groups. At 10 days hematocrit values were significantly lower in the two highest lead treated groups, and hemoglobin content and red blood cell delta-aminolevulinic acid dehydratase (ALAD) activity was depressed in all lead treated groups. Plasma creatine phosphokinase decreased in the two highest treatment groups. Brain, liver and kidney ALAD activities, brain RNA to protein ratio and liver protein concentration decreased after lead exposure whereas liver DNA, DNA to RNA ratio and DNA to protein ratio increased. Brain monoamine oxidase and ATPase were not significantly altered. Measurements of the ontogeny of hematological variants and enzymes in normal development, using additional untreated nestlings, revealed decreases in red blood cell ALAD, plasma aspartate amino transferase, lactate dehydrogenase, brain DNA and RNA and liver DNA, whereas hematocrit, hemoglobin, plasma alkaline phosphatase, brain monoamine oxidase, brain ALAD and liver ALAD increased during the first 10 days of posthatching development. Biochemical and hematological alterations were more severe than those reported in adult kestrels or precocial young birds exposed to lead. Alterations may be due in part to delayed development.